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Biomedical subjects

B Dobbs

Publications and source records attributed to B Dobbs.

11 recordsLinked to original sources
PubMed2001

The use of 3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-methoxy-4-methylcoumarin (AMMC) as a specific CYP2D6 probe in human liver microsomes.

Recently, a novel nonfluorescent probe 3-[2-(N,N-diethyl-N-methylammonium)-ethyl]-7-methoxy-4-methylcoumarin (AMMC), which produces a fluorescent metabolite AMHC (3-[2-(N,N-diethyl-N-methylammonium)ethyl]-7-hydroxy-4-methylcoumarin) was used with microsomes containing recombinant enzymes (rCYP) to monitor CYP2D6 inhibition in a microtiter plate assay. This article describes the studies that were performed in human liver microsomes (HLM) to establish the selectivity of AMMC toward CYP2D6. Metabolism studies in HLM showed that AMMC was converted to one metabolite identified by mass spectrometry as AMHC. Kinetic studies indicated an apparent K(m) of 3 microM with a V(max) of 20 pmol/min. mg of protein for the O-demethylation reaction. The O-demethylation of AMMC in HLM was inhibited significantly in the presence of a CYP2D6 inhibitory antibody. Using a panel of various HLM preparations (n = 12), a good correlation (r(2) = 0.95) was obtained between AMMC O-demethylation and bufuralol metabolism, a known CYP2D6 substrate, but not with probes for the other major xenobiotic metabolizing CYPs. Finally, only rCYP2D6 showed detectable metabolism in experiments conducted with rCYPs using AMMC at a concentration of 1.5 microM (near K(m)). However, at a concentration of 25 microM AMMC, rCYP1A also contributed significantly to the formation of AMHC. Knowing the experimental conditions under which AMMC was selective for CYP2D6, a microtiter assay was developed to study the inhibition of various compounds in HLM using the fluorescence of AMHC as an indication of CYP2D6 activity. The inhibition potential of various chemicals was found to be comparable to those determined using the standard CYP2D6 probe, bufuralol, which requires high-performance liquid chromatography separation for the analysis of its CYP2D6-mediated 1'-hydoxylated metabolite.

Coumarins↗
PubMed1996

Dehydroepiandrosterone and cardiac allograft vasculopathy.

BACKGROUND: Tissue culture, animal model, and epidemiologic studies suggest that dehydroepiandrosterone may inhibit atherosclerosis through its potent antiproliferative effects. Because cardiac allograft vasculopathy is predominantly a proliferative abnormality of intimal and medial smooth muscle cells, plasma levels of dehydroepiandrosterone may play an important role in the development of this disease. METHODS: Sixty-one cardiac allograft recipients who survived for 1 year or more and had at least one annual follow-up cardiac catheterization were included in the study. Plasma levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and free dehydroepiandrosterone (dehydroepiandrosterone not bound to sex hormone-binding globulin) were measured in all 61 subjects and compared with the presence or absence of cardiac allograft vasculopathy as defined by angiography. RESULTS: Plasma levels of total and free dehydroepiandrosterone were lower in subjects in whom cardiac allograft vasculopathy developed (p = 0.005 and 0.003, respectively). Furthermore, the time to development of cardiac allograft vasculopathy was shorter in subjects with low levels of total and free dehydroepiandrosterone (p = 0.062 and 0.046, respectively). This relationship was maintained after adjusting for age, gender, cholesterol, prednisone use, and blood pressure. CONCLUSIONS: Low plasma levels of dehydroepiandrosterone may facilitate and high levels may retard the development of cardiac allograft vasculopathy.

Adult↗
PubMed1990

LaPorta great toe implant. Long-term study of its efficacy. Student Research Group.

The purpose of this study was to evaluate the long-term function of the LaPorta design great toe implant. Eight cases were evaluated preoperatively and on a short-term (mean = 3.6 months) and a long-term basis (mean = 20.5 months) postoperatively. Findings of clinical importance included decreased hallux dorsiflexion and radiographic evidence of hyperostosis formation at the implant hinge. However, all of the patients studied were satisfied with their results.

Aged↗
PubMed1988

African American adolescents: adaptational processes and socioeconomic diversity in behavioural outcomes.

The study was concerned with determining the relationship of economic diversity to stress reactivity. Parental ratings of competence and behavioural problems were obtained for very young adolescents following a long-term and highly acute stress: the Atlanta youth murders. Intellectual and identity-formation data obtained both before and after the crisis were analyzed with the parental ratings of youth competence and behavioural problems. Consistent socioeconomic status (SES) links between the manifestation of behavioural problems and the display of competencies were obtained; lower income (LI) youths manifested more problems and fewer competencies. The findings were more pronounced for LI males. Personal identity was a significant predictor of school competence. School self-esteem was a predictor of academic performance. The manifestation of behavioural problems was significantly predicted by cognitive performance variables. The findings are discussed in terms of variations in adaptational strategies mediated by socioeconomic status and psychological factors.

Achievement↗
PubMed1984

Epidemiological study of psychiatric disorder in adolescent girls: preliminary communication.

A two-stage general population study of affective disorder and problems of eating control in 15-19-year-old girls is in progress, the sample being identified by the use of general practitioners' age-sex registers. So far, 244 girls and their mothers have been interviewed and have independently completed questionnaires relating to mood and appetite control. The girls completed questionnaires both on themselves and on their mothers, and their mothers on themselves and on their daughters. Significant correlations between self-rating and rating of the other person were obtained in all cases, with agreement on the daughters' mood being higher in non-manual couples.

Adolescent↗
PubMed1980

High perfusion pressure damages the sieving ability of sinusoidal endothelium in rat livers.

Fenestrated endothelium lining liver sinusoids forms an ultrastructural sieve between blood and hepatocytes which at physiological perfusion pressures has previously been shown to shield hepatocytes from large triglyceride-rich chylomicrons. In the study reported in this paper, enlargement of endothelial fenestrae at high perfusion pressures has been confirmed and a concurrent increase in trapping of large chylomicrons by the liver noted. These findings suggest the importance of employing physiological perfusion pressures in studies designed to examine hepatic lipoprotein metabolism and also suggest a possible mechanism in the pathogenesis of fatty change seen in the "nutmeg" liver of chronic venous congestion.

Animals↗
PubMedDate not supplied

A double-blind crossover study comparing two doses of Duranest (etidocaine) 1% with a fixed dose of Sensorcaine (bupivacaine) 0.5% utilizing infiltration regional blocks of the fifth ray.

Two local anesthetics, Duranest 1% (etidocaine HCl) and Sensorcaine 0.5% (bupivacaine HCl), were tested against each other in dose-related blocks of the fifth ray. This study was conducted under double-blind cross-over conditions using 24 healthy volunteers. It was found that 4 ml. of either agent was sufficient to anesthetize the fifth ray area in all but 4.2% of the injections and 8 ml. of etidocaine always accomplished complete fifth ray anesthesia. Also, 4 ml. of etidocaine was found to have a more rapid onset and longer duration than the same volume of bupivacaine, 6.3 vs. 8.3 min. onset, and 487 vs. 449 min. duration, respectively. Pain and burning upon injection of either bupivacaine or etidocaine was encountered in 70% of the subjects tested. Residual pain was noted in some of the subjects given etidocaine after complete resolution of sensory anesthesia. Residual pain was not noted in any of the subjects given bupivacaine. Etidocaine was found to have a more rapid onset and a longer duration than bupivacaine or a lidocaine-bupivacaine mixture, and was thus found to be a superior agent in the subjects tested.

Acetanilides↗